Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8⁺ T-cell responses in melanoma patients.

Abstract

Optimal vaccine strategies must be identified for improving T-cell vaccination against infectious and malignant diseases. MelQbG10 is a virus-like nano-particle loaded with A-type CpG-oligonucleotides (CpG-ODN) and coupled to peptide(16-35) derived from Melan-A/MART-1. In this phase IIa clinical study, four groups of stage III-IV melanoma patients were vaccinated with MelQbG10, given (i) with IFA (Montanide) s.c.; (ii) with IFA s.c. and topical Imiquimod; (iii) i.d. with topical Imiquimod; or (iv) as intralymph node injection. In total, 16/21 (76%) patients generated ex vivo detectable Melan-A/MART-1-specific T-cell responses. T-cell frequencies were significantly higher when IFA was used as adjuvant, resulting in detectable T-cell responses in all (11/11) patients, with predominant generation of effector-memory-phenotype cells. In turn, Imiquimod induced higher proportions of central-memory-phenotype cells and increased percentages of CD127(+) (IL-7R) T cells. Direct injection of MelQbG10 into lymph nodes resulted in lower T-cell frequencies, associated with lower proportions of memory and effector-phenotype T cells. Swelling of vaccine site draining lymph nodes, and increased glucose uptake at PET/CT was observed in 13/15 (87%) of evaluable patients, reflecting vaccine triggered immune reactions in lymph nodes. We conclude that the simultaneous use of both Imiquimod and CpG-ODN induced combined memory and effector CD8(+) T-cell responses.

• Authors: Simone M Goldinger, Reinhard Dummer, Petra Baumgaertner, Daniela Mihic-Probst, Katrin Schwarz, Anya Hammann-Haenni, Joerg Willers, Christine Geldhof, John O Prior, Thomas M Kündig, Olivier Michielin, Martin F Bachmann, Daniel E Speiser
• Journal: European journal of immunology (Eur J Immunol) Vol. 42 Issue 11 Pg. 3049-61 (Nov 2012) ISSN: 1521-4141 [Electronic] Germany
• PMID: 22806397 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Adjuvants, Immunologic
• Aminoquinolines
• CPG-oligonucleotide
• Cancer Vaccines
• Ligands
• Lipids
• MART-1 Antigen
• Oligodeoxyribonucleotides
• TLR7 protein, human
• TLR9 protein, human
• Toll-Like Receptor 7
• Toll-Like Receptor 9
• incomplete Freund's adjuvant
• Freund's Adjuvant
• Imiquimod

Topics

• Adjuvants, Immunologic (administration & dosage)
• Aminoquinolines (administration & dosage)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (administration & dosage, adverse effects, immunology)
• Flow Cytometry
• Freund's Adjuvant (administration & dosage)
• Humans
• Imiquimod
• Immunologic Memory (immunology)
• Ligands
• Lipids (administration & dosage)
• MART-1 Antigen (immunology)
• Melanoma (immunology, therapy)
• Nanoparticles (administration & dosage)
• Oligodeoxyribonucleotides (immunology)
• Skin Neoplasms (immunology)
• Statistics, Nonparametric
• Toll-Like Receptor 7 (immunology)
• Toll-Like Receptor 9 (immunology)